Intravascular Cerebral Catheter Device and Method of Use

ABSTRACT

Cerebral Catheter devices and methods for use are provided. The catheter devices provided may include an anti-thrombotic agent coating on the exterior surface. The catheter devices may include unique tip configurations to allow improved fluid delivery capabilities. Further, the catheter devices may also or alternatively include one or more sensor devices in communication with a controller that allow automatically adjusting the delivery of a therapeutic fluid, for example a vasodilator, in response to the condition sensed by the catheter device, such as increased pressure. Moreover, the catheter devices may also be used in conjunction with blood flow transducers to detect and timely prevent and treatment vasospasms or other conditions. Methods for preventing and treatment vasospasm, neoplasm, or other pathological conditions while prolonged using the catheter device are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 12/876,786filed on Sep. 7, 2010, which is a continuation of PCT/US2009/038071filed on Mar. 24, 2009, which claims priority benefit of U.S.Provisional Application No. 61/038,922, filed Mar. 24, 2008, the entirecontents of which are incorporated by reference herewith.

FIELD OF THE INVENTION

The present invention relates generally to medical devices, and moreparticularly to cerebral intravascular catheter devices, and methods ofuse, for treating cerebral vasospasms and neoplasms, particularly brainglioblastomas.

BACKGROUND OF THE INVENTION

Catheters have many medical uses. Among these uses are delivery ofintravenous fluids, administering chemotherapy to a particular organ orsite, and to assist in cardiac procedures and for treating coronaryartery deficiencies. Catheters are also being used during neurosurgicalprocedures for the treatment of cerebral vasospasms, which may lead tocerebral ischemia.

However, in any of the above-described uses of catheters, thrombosis andthe development of embolisms are a concern when used for extendeddurations. Embolic phenomenon, which may result from thrombosis, canlead to tissue damage. Maintaining catheterization for extendeddurations carries significant advantages, such as making available moretypes of treatment and medicines to the patient, broadening the types ofconditions that may be treated rather than by ways of more invasiveprocedures, improving the effectiveness of treatment due to longertreatment durations, and adjusted treatment cycles, for example.

Avoiding thrombosis or embolic phenomena are particularly important inthe treatment of cerebral vasospams. It has been shown thatintravascular infusion of verapamil and other substances can minimizecerebral vasospasm. Unfortunately, the catheter cannot be left in situfor a long period of time to treat this relatively chronic condition,thus, suboptimal drug delivery results.

Accordingly, there exists a need for improved catheter devices andmethods for using the same. More specifically, there exists a furtherneed for neurological or cerebral intravascular catheter devices andmethods for treating cerebral vasospasms and avoiding thrombosis orembolic phenomenon before, during, and after neurosurgery.

SUMMARY OF THE INVENTION

Catheter devices, particularly neurological or cerebral intravascularcatheter devices, and methods of use for preventing and/or treatingvasospasm, neoplasm, thrombosis or other embolic phenomenon, as well ascatheter-induced infections are provided. In certain embodiments, theintravascular catheter devices provided for neurosurgery or brainsurgery or other physiological or pathological situations, may be coatedon the exterior surface with a matrixes with protein or othersubstances, such as an anti-thrombotic agent and/or vasodilator. Inother embodiments, the intravascular catheter devices may include uniquedistal tip configurations to allow for improved fluid or drug deliverycapabilities to timely release therapeutic fluid containing one or moretherapeutic agents for desired treatment. In one embodiment, thetherapeutic agent is an anti-thrombosis agent or anticoagulant thatwould minimize the development of thrombosis and thus diminish thedanger of embolic tissue damage. In yet another embodiment, thetherapeutic agent is an antibiotic that would treat catheter-inducedinfection. In yet another embodiment, the therapeutic agent is achemotherapeutic agent for treating neoplasms. In certain embodiments,the catheter device is configured for insertion into the neuralvasculature.

In further embodiments, the intravascular catheter devices may also, oralternatively, include one or more sensor devices in communication witha controller that allow automatically adjusting the delivery of atherapeutic fluid, for example, a vasodilator, in response to acondition sensed by a sensor device of the catheter. In furtherembodiments, the intravascular catheter devices may be used inconjunction with external monitoring devices, such as a blood flowtransducer, to monitor velocity in blood vessels and provide real timevasospasm detection, therefore, allowing time release or delivery of atherapeutic agent to prevent vasospasms, thrombosis, or other embolicphenomenon.

The invention provides a catheter device that allows for prolongedinsertion and treatment by including an anti-thrombotic agent oranticoagulant coating to reduce the likelihood of causing thrombosis. Inanother aspect, the invention includes providing a catheter with sensorsthat allow sensing certain conditions at or near the procedure site,which further allow a controller to adjust the delivery of a medicinalagent, such as a vasodilator. Accordingly, a catheter device includingone or more sensors of this type allow for quick detection of vasospasmactivities and immediate treatment thereof.

According to one embodiment of the invention, a catheter device isprovided having a distal end and a proximal end, and also having atleast one lumen extending from the proximal end to the distal end of theelongate catheter body. An anti-thrombotic agent may be deposited on atleast part of the exterior surface of the elongate catheter body. In anexemplary embodiment, the anti-thrombotic agent comprises a coatingapplied to substantially the entire exterior surface of the elongatecatheter body, or alternatively, the anti-thrombotic agent comprises acoating applied to a portion of the elongate catheter body extendingproximally from the distal end. Yet further, the anti-thrombotic agentmay be at least partially impregnated into the material comprising theelongate catheter body. In another example embodiment, theanti-thrombotic agent may be time releasable. Another aspect of thisembodiment may include an anti-thrombotic agent coating at leastpartially on the interior surface of the catheter within the lumen.

According to another examplary embodiment, the catheter device mayinclude an elongate catheter body having a distal end and a proximalend, and also having at least one lumen extending from the proximal endto the distal end of the elongate catheter body. Further, in thisembodiment, a perforated tip may be affixed to the distal end of theelongate catheter body. The perforated tip may include a plurality ofperforated orifices extending through the perforated tip and in fluidcommunication with the lumen or lumens. In one embodiment, the distalcatheter may be placed at the most distal part of the internal carotidartery.

Another aspect of this embodiment may include the catheter device havinga first and a second lumen extending from the proximal end to the distalend of the elongate catheter body, wherein the perforated tip furthercomprises at least one central orifice in communication with the firstlumen, and wherein the plurality of perforated orifices are in fluidcommunication with the second lumen. In this example, a secondarymedical device may be passed through the first lumen and the at leastone central orifice. For example, the secondary medical device mayinclude a guide wire or a balloon.

Another aspect of this embodiment may include the catheter device havingat least one fluid that is delivered through the at least one lumen andthe plurality of perforated orifices. The fluid may be, for example, asaline solution or a composition solution comprising a vasodilator, ananti-thrombotic agent, an anticoagulant, an antibiotic, achemotherapeutic agent, or any other therapeutic agents.

According to yet a further embodiment of the invention, a catheterdevice is provided that includes an elongate catheter body, having adistal end and a proximal end, and also having at least one lumenextending from the proximal end to the distal end of the elongatecatheter body. A catheter device according to this embodiment mayfurther include at least one sensor device affixed to the elongatecatheter body substantially near the distal end and in electricalcommunication with a controller, and a fluid delivery device in fluidcommunication with the at least one lumen and in electricalcommunication with the controller. The controller may be operable toexecute instructions to: receive at least one signal from the at leastone sensor device, perform an analysis on the at least one signal, andgenerate a signal to adjust fluid delivery to the at least one lumenfrom the fluid delivery device, responsive at least partially to theanalysis performed.

An aspect of this embodiment may include a catheter device where the atleast one sensor device comprises a pressure sensor device operable tosense pressure in the fluid at or near the distal end of the catheterdevice. Alternatively, another aspect of this embodiment may include thecatheter device where the at least one sensor device comprises a distalsensor device, and further including a proximal sensor device affixed tothe elongate catheter body proximal the distal sensor device and incommunication with the controller. The distal sensor device may generatea first signal corresponding to a distal pressure and the proximalsensor device may generate a second signal corresponding to a proximalpressure.

For example, the analysis performed by the controller may comprisecomparing the distal pressure to the proximal pressure, and wherein ifthe distal pressure is at a predefined limit greater than the proximalpressure, the signal to adjust fluid delivery causes an increase in thefluid delivery, and wherein if the distal pressure is at a predefinedlimit lower than the proximal pressure, the signal to adjust fluiddelivery causes a decrease in the fluid delivery. In another example,the analysis performed by the controller may include determining a ratioof the distal pressure to the proximal pressure, and wherein if theratio is at or exceeds a first predefined limit, the signal to adjustfluid delivery causes an increase in the fluid delivery, and wherein ifthe ratio is below a second predefined limit, the signal to adjust fluiddelivery causes a decrease in the fluid delivery. The fluid deliverydevice may deliver, for example, a vasodilator, an anti-thrombosisagent, a chemotherapy agent, or other therapeutic agent as needed.

According to another aspect of this embodiment, the at least one sensordevice may be a flow sensor device operable to assess a flow rate of thefluid at or near the distal end of the catheter device. An aspect ofthis embodiment may include a catheter device where the at least onesensor device comprises a blood flow transducer operable to monitor andassess blood flow velocity in the major arteries on a real time,beat-to-beat basis at or near the distal end of the catheter device. Incertain embodiment, an ultrasound probe may be attached to the primarycatheter to monitor blood flow speed thereby discovering the presence ofvasospasm.

According to yet another embodiment of the invention, a method for usinga catheter device is provided. The method may include sensing by atleast one sensor device a condition at at least one location in a vesselin which the catheter is positioned, transmitting at least one signal toa controller from the at least one sensor device corresponding to thecondition sensed, performing an analysis on the at least one signal, andadjusting a fluid delivery device in communication with the catheterdevice responsive at least in part to the analysis performed on the atleast one signal. In one example, the method may include sensing acondition substantially near a distal end of the catheter device by adistal sensor device and sensing a condition proximal to the distal endby a proximal sensor device, wherein the analysis includes comparing thecondition sensed by the distal sensor device to the condition sensed bythe proximal sensor device.

According to one aspect of this embodiment, the fluid delivery may beadjusted by increasing fluid delivery if the condition sensed at thedistal sensor device is greater than the condition sensed by theproximal sensor device, and decreasing fluid delivery if the conditionsensed at the distal sensor device is lower than the condition sensed bythe proximal sensor device.

According to yet another embodiment of the invention, a method for usinga catheter device for treating vasospasm is provided. The method mayinclude coating the endovascular catheter of the present invention withan anti-thrombotic agent or anticoagulant, such as heparin, inconjunction with other therapeutic agents, including, but not limitedto, antibiotic, vasodilator, and chemotherapeutic agent; inserting thecoated endovascular catheter into the appropriate location; and timelyreleasing the therapeutic agents as needed. In certain embodiments, themethod of the present invention uses an endovascular catheter devicethat comprises a catheter tip that may be fashioned like a shower headwith one central lumen in which the wire is used to pass the catheter inthe correct position. The catheter tip may include a number of smalleropenings that allow fluid comprising one or more therapeutic agents,such as anti-thrombosis agent, anticoagulant, vasodilator, antibiotic,and chemotherapeutic agent, to exit the catheter at a higher pressure.In one embodiment, the catheter of the present invention is a cerebralcatheter configured to be inserted into cerebral arteries to prevent andtreat cerebral vasospasm, brain neoplasms (e.g., brain glioblastomas),or other pathological conditions associated with prolonged use of acatheter device.

In yet anther embodiment of the invention, the method of the presentinvention uses an endovascular catheter device that comprises acybernetic loop for management of cerebral vasospasm in which the distalportion of the catheter is placed in an appropriate location. The methodcomprises placing a transducer that monitors blood pressure or velocityat a location near the tip of the catheter; placing another transducerlocated proximally in the systemic circulation which also records bloodpressure or velocity; and connecting a pump to the catheter, operable ina cybernetic fashion, wherein the pump increases the flow of avasodilator or other vasogenic substance into the area of vasospasm whenthe ratio of the distal blood pressure or velocity and proximal bloodpressure or velocity increases, and wherein the pump diminishes the flowof pumping the vasodilator or other vasogenic substance into the area ofvasospasm when the ratio between the distal blood pressure or velocityand proximal blood pressure or velocity decreases toward normality. Inone embodiment, the vasodilator is verapamil. In yet another embodiment,other therapeutic agents, such as antibiotic and chemotherapeutic agentscan also be used in conjunction with the vasodilators or other vasogenicsubstances to prevent or treat catheter induced infections andneoplasms. The present invention also provides a method of using thecatheter devices in conjunction with an externally located blood flowtransducer to detect, prevent, and treat vasoplasms, neoplasms, or otherpathological conditions associated with prolonged use of the catheterdevices.

In yet another embodiment of the invention, the method of the presentinvention uses any of the above endovascular catheter devices to injectchemotherapeutic agents into neoplasms, particularly those located inthe brain such as glioblastomas. The appropriate feeding vessel can becatheterized and the chemotherapeutic agent can be delivered slowly overa prolonged period of time at a routinely programmed rate.

BRIEF DESCRIPTION OF THE DRAWINGS

The objects and advantages of the invention will be better understoodand more readily apparent when considered in conjunction with thefollowing detailed description and accompanying drawings whichillustrate, by way of example, embodiments of the catheter device andmethods of using the same and in which:

FIGS. 1A-B are schematic views of the catheter device, according to oneexample embodiment of the invention. FIG. 1A illustrates a partial viewof the catheter device, according to one example embodiment of theinvention. FIG. 1B illustrates a lateral cross-section view of thecatheter device of FIG. 1A, taken across line 1-1, according to oneexample embodiment of the invention.

FIG. 2 illustrates a partial distal end view of the catheter device,according to one example embodiment of the invention.

FIG. 3 is a functional diagram of the catheter device, according toanother example embodiment of the invention.

FIG. 4 is a functional flow diagram representing a method of operatingthe catheter device, according to an example embodiment of theinvention.

DETAILED DESCRIPTION OF THE INVENTION

As required, detailed embodiments of the invention are disclosed herein;however, it is to be understood that the disclosed embodiments aremerely exemplary of the invention which may be embodied in variousforms. Therefore, specific structural and functional details disclosedherein are not to be interpreted as limiting, but merely as a basis forthe claims and as a representative basis for teaching one skilled in theart to variously employ the present invention in virtually anyappropriately detailed structure.

The present invention provides a catheter device, and method of usethereof, for preventing and treating vasospasm, formation of thrombosisor other embolic phenomenon, catheter induced infections, and neoplasms.

Catheter devices may be used during neurosurgical procedures for thetreatment of conditions existing in the cerebrum. One use of a catheterdevice during neurosurgical procedures is during the treatment ofcerebral vasospasms. For example, a catheter may be used to selectivelydeliver a vasodilating agent to the vasospastic site. In anotherexample, a catheter may be used to mechanically dilate the vessel, suchas by the use of a balloon tip during angioplasty procedures. Though,because of the potential that the catheter may become thrombosed duringthe procedure, limiting the duration of catheter use in the patient, theabove-mentioned therapeutic procedures have been limited. Often, theduration during which the catheter should be inserted for optimumtreatment is longer than a safe period to avoid causing thrombosis inthe vasculature.

A catheter device for use in neurosurgical procedures (as well as otherprocedures), as described herein, has been developed to overcome thedifficulties previously described. The catheter device may include acoating or a matrix layer comprising protein or other anti-thromboticagents infused therein. In one example, the anti-thrombotic coating orlayer may include a time-release mechanism, whereby the release of theanti-thrombotic agent may be controlled over time. The coating may beapplied at least partially to the exterior surface of the catheterdevice, and optionally may be applied to at least partially to theinterior surface of the catheter making up one or more lumens or ports.It is appreciated that additional medicinal agents may be included inthe coating or layer, such as, but not limited to, antibiotics, aspirin,heparin, warfarin, anticoagulants, vasodilators, or chemotherapeuticagents. The anti-thrombotic agent (or other coating) may be impregnatedinto the catheter device via a protein colloidal matrix.

As used herein, anti-thrombotic agents are used interchangeably withanticoagulant, both refer to therapeutic agents that are capable ofpreventing and/or treating thrombosis and embolic phenomenon. Thrombosisrefers to a formation of a blood clot (thrombus) inside a blood vessel,obstructing the flow of blood through the circulatory system.Embolisation occurs when a bacterial infection is present at the site ofthrombosis, the thrombus may break down, spreading particles of infectedmaterial throughout the circulatory system (pyemia, septic embolus) andsetting up metastatic abscesses wherever they come to rest. Without aninfection, the thrombus may become detached and enter circulation as anembolus, finally lodging in and completely obstructing a blood vessel,which unless treated very quickly will lead to tissue necrosis (aninfarction) in the area past the occlusion. If the occlusion is in thecoronary artery, myocardial ischemia is likely to occur, whereby cardiacmyocytes cannot function properly due to lack of oxygen. This lack ofoxygen is then likely to result in a myocardial infarction. A stroke iscause by cerebral infarction resulted from a disturbance in the bloodvessels supplying blood to the brain. Exemplary anti-thrombolic agentsor anticoagulants include, but are not limited to, heparin andderivative substances including low molecular weight heparin, vitamin Kantagonist, warfarin, and derivative substances, and syntheticpentasaccharide inhibitors of factor Xa such as fondaparinux andidraparinux.

As used herein, vasodilators refer to drugs that relax the smooth musclein blood vessels, which causes the vessels to dilate. Vasodilators canbe classified based on their site of action (arterial versus venous) orby mechanism of action. Some vasodilators primarily dilate resistancevessels (arterial dilators; e.g., hydralazine), while others primarilyaffect venous capacitance vessels (venous dilators; e.g.,nitroglycerine). Most vasodilator drugs, however, have mixed arterialand venous dilator properties (mixed dilators; e.g., alpha-adrenoceptorantagonists, angiotensin converting enzyme inhibitors). In oneembodiment, the vasodilator is verapamil.

In another example embodiment, the catheter device may also include aperforated tip connected to its distal end or distal region. Theperforated tip may provide an improved distribution of fluid flow fromwithin the catheter. Additionally, the perforated tip may allow fluid tobe delivered to the site at a higher pressure. By increasing the fluidflow and/or increasing the pressure at which the fluid is delivered,clotting will be reduced at the site. The fluid being delivered may be,in one example, a saline solution. In another example, the fluid beingdelivered may be, either alone or in combination with other fluidscomprising other therapeutic agents, such as an anti-thrombotic agent orother anticoagulant to reduce the likelihood of forming a thrombus atthe site or on the catheter, a vasodilator to treat vasospasms occurringat the site, an antibiotic to treat catheter-induced local or systemicinfections, or a chemotherapeutic agent to treat neoplasm. Furthermore,it is appreciated that this embodiment may further include ananti-thrombotic agent coating on all or part of the surface of thecatheter body and optionally on the interior surface of the cathetermaking up the lumen.

In another example embodiment, the catheter device may include at leastone sensor device positioned at or near the distal portion of thecatheter device. In one example, the sensor device may be a pressure orblood flow velocity sensor device. The pressure sensor device maycommunicate the pressure existing in the vessel near the distal portionof the catheter to an adjustable controller, which may then adjust thedelivery of a vasodilator to the site based upon the pressure measured.The combination of one or more pressure sensing devices in communicationwith the controller may allow for implementing a feedback loop (orcybernetic loop) between the pressure sensed at the site (for example,the vasospasm site) and the delivery of the agent and/or any otherfluids to the site. For example, the greater the pressure, the greaterthe delivery of the vasodilator to the site. Alternatively, sensing adecreased or a decreasing pressure at the site may cause the controllerto deliver less vasodilator.

In another embodiment, the catheter device may include two pressuresensing devices, both in communication with a controller. The firstpressure sensing device may be positioned at or near the catheter'sdistal portion, as previously described, and the second pressure sensingdevice may be positioned proximal from the first pressure sensingdevice, for example in the systemic vasculature. Having two pressuresensing devices allows for the controller to perform a relativecomparison between the pressure measured in the vasculature at or nearthe procedure site and the pressure at another point in the patient'svasculature. The relative comparison allows the controller to adjust thedelivery of the vasodilator (or other agents) based on the differencebetween the two measured pressures. It is appreciated that the twomeasured pressures may be compared in many ways, for calculating thedifference, calculating a ratio, modeling, adaptive, real-time learning,mathematical algorithms, or the like. It is also appreciated that theoperator of the catheter, for example the physician performing theprocedure, may also observe the measured pressure at the first or boththe first and the second locations as displayed by the controller andperform the adjustments manually.

The catheter device may also include, in addition to or alternatively,other sensing devices at or near the distal portion of the catheter toaid in sensing the environment at or near the procedure site. In oneexample embodiment, the catheter device may include an ultrasonicmonitoring device at or near the distal portion of the catheter deviceand in communication with a controller. The ultrasonic monitoring devicemay be used to monitor blood flow rate at or near the site, which may beindicative of the presence and/or severity of a vasospasm in the vessel.As described in reference to the pressure sensing devices, the flow ratemeasurements obtained from the ultrasonic monitoring device may besupplied to the controller for adjusting the delivery of fluid, such asvasodilators, or alter other treatment being provided by the catheter.It is appreciated that these embodiments including sensor devices mayfurther include an anti-thrombotic agent coating on all or part of thesurface of the catheter body and optionally on the interior surface ofthe catheter making up the lumen.

In one embodiment, an ultrasonic monitoring device is a transducer thatis implanted, recessed into, or temporarily attached to patient's skull.Such a transducer can be used in conjunction with the cerebral catheterof the invention to assess blood flow velocity in the major basalintracranial arteries on a real-time, beat-to-beat basis. Blood flowvelocity is calculated and used to make determinations aboutintracranial hemodynamics. The blood flow velocity obtained from theultrasonic transducer can be supplied to the controller for adjustingthe delivery of the therapeutic fluid comprising desired therapeuticagents as described above, particularly for treating cerebralvasospasms, thrombotic and embolic phenomenon, catheter-inducedinfections, or neoplasms. The neurological or cerebral catheters of theinvention are particularly configured to be inserted into majorintracranial arteries before, during, or after neuro- and/or brainsurgery. Methods of implanting or attaching the transducer to thepatient's skull are well known in the art. For instance, the transducerattached to a helmet or a head-band that can be wore by the patient. Thetransducer can also be implanted or screwed onto patient's skull.

In one embodiment, the ultrasonic transducer used in conjunction withthe catheter device of the invention can be a Transcranial Doppler (TCD)(developed by Multigon, Texas). The cranial catheters of the presentinvention in conjunction with TCD can be used to evaluate intracranialeffects of extracranial lesions, including information oncollateralizing channels and tandem stenoses. In addition, the cranialcatheters of the present invention in conjunction with TCD allows directperioperative evaluation of middle cerebral artery blood flow velocityin carotid endarterectomy patients, and to monitor for re-occlusion andhyperperfusion syndrome. Furthermore, the cranial catheters of thepresent invention in conjunction with TCD is also used to detect andclassify intracranial emboli in view of the appearance of high intensitytransient signals in the TCD waveform as indicators of circulatingmicroemboli. Other applications of the cranial catheters of the presentinvention in conjunction with TCD also include the early(sub-angiographic) bedside detection of vasospasm in subarachnoidhemorrhage patients, evaluation of stroke and transient ischemic attack,as an adjunct in the assessment of cerebral circulatory arrest, and as amonitoring tool for patients undergoing intracranial interventionalprocedures. The present invention also encompasses the use of theadditional catheter devices, particularly neurological or cerebralcatheter devices, in conjunction with other blood flow transducers ordiagnostic modalities, for monitoring and assessing intracranialhemodynamics, allowing a physician or controller for adjusting timelyrelease or delivery of appropriate therapeutic agents at the cathetersite over an extended period of time.

Although the catheter device has been described in detail above asdelivering a vasodilator and/or anti-thrombotic agent, it is appreciatedthat other medicinal and/or therapeutic agents may be delivered by thecatheter device in much the same manner as described herein. Therefore,in one embodiment, the catheter device may be used to aid in thedelivery of chemotherapeutic agents, such as a bevacizumab, to neoplasmsor other tumorous conditions. A catheter device having a coating orlayer of anti-thrombotic agents applied to its elongate body, orconfigured to deliver anti-thrombotic agents to the site, as furtherdescribed herein for extended indwelling, allows for longer durationprocedures and more effective delivery of chemotherapeutic agents. Inone example, the catheter device may be configured to deliverchemotherapeutic agents to the glioblastoma sites. Though, it isappreciated that a catheter configured for the delivery ofchemotherapeutic agents may be used for any type of neoplasm or tumorouscondition, and is not limited by this example description toglioblastoma sites. The examplary catheter device may inserted anddirected to the neoplasm site, and used to deliver one or morechemotherapeutic agents over longer durations than were previouslyavailable. Furthermore, the chemotherapeutic agent may be released overtime to the neoplasm site or in periodic dosages, such as on for apredefined period and off for a predefined period and back on, overtime. The catheter device may also be configured to communicate with acontroller to control the delivery of the chemotherapeutic agent. Ananti-thrombotic layer or coating may allow keeping the catheter insertedfor longer periods of time, allowing for longer durations ofchemotherapeutic agent administration.

Example catheter devices can further be understood with reference to theexample, non-limiting embodiments illustrated in FIGS. 1-4.

FIG. 1A illustrates an example embodiment of a catheter device 100including an anti-thrombotic agent coating or layer on its exteriorsurface. The catheter device 100 may be an elongate catheter body 110for insertion through a patient's vasculature and delivery to a diseaseor symptomatic site. In one example, the catheter device 100 may be usedduring the treatment of a vasospasm in a vessel. The vasospasm mayexist, for example, in the patient's cerebral vasculature. The elongatecatheter body 110 may be constructed from a semi-rigid to pliablematerial to ease both in the insertion and guiding to the proceduresite. For example, the elongate catheter body 110 may be constructedfrom a material that is substantially rigid at room temperature, butbecomes pliant as exposed to higher temperatures, such as the patient'sbody temperature. The catheter body 110 may optionally include materialthat causes the catheter device 100 to be radiopaque and/or include oneor more markers such as fluoroscopic or radiopaque markers used to helplocate and guide the catheter.

It is appreciated that the size of the elongate catheter body 110 mayvary, depending upon its intended use. In one example, a catheter device100 intended for delivery to the cerebral vasculature may have adiameter between approximately 0.25 millimeters and approximately 1.0millimeters (or, for example, approximately 1 Fr. to 3 Fr.). However, itis appreciated that other catheter devices used with this invention mayhave greater or smaller diameters. The catheter device may be insertedthrough a femoral artery or subclavian vein. In some exampleembodiments, the catheter device is delivered to the cerebralvasculature, for example the distal portion of the carotid artery, forthe treatment of cerebral vasospasms and the like.

The catheter device 100 may further include an anti-thrombotic agentcoating 120 on its exterior surface, or alternatively an anti-thromboticagent layer as the exterior surface may be formed as part of thecatheter device. The anti-thrombotic agent coating/layer 120 mayinclude, for example, heparin, or a mixture of heparin and othertreatment agents or substances. In one example, in addition toanti-thrombotic agents, one or more antibiotic substances may beincluded in the layer 120. In another example, the anti-thrombotic agentcoating 120 may be formed as part of a matrix, for example, a proteinmatrix, a colloidal matrix, or a protein colloidal matrix, as is known.The anti-thrombotic layer 120 may be applied to substantially the entirelength of the catheter, or may be applied only to specific areas inwhich the likelihood of thrombosis are greater. In another example, anadditional anti-thrombotic layer may be at least partially applied tothe interior surface of the catheter device 100. Including ananti-thrombotic layer in the interior surface of the catheter device 100allows for the release of the agent as fluid or other devices aredelivered therethrough. Additionally, the anti-thrombotic coating orlayer may include a time-release mechanism, whereby the release of theanti-thrombotic agent may be controlled over time.

The anti-thrombotic agent allows for keeping the catheter deviceinserted for prolonged periods, making available additional proceduresand treatments. For example, a time released anti-thrombotic agentcoating or layer may allow for using the catheter device in patient forup to approximately ten days. In some applications, for example duringneurosurgical procedures, a catheter device including an anti-thromboticagent may be inserted before or during the neurosurgical procedure, toallow detecting and treating a vasospasm. Alternatively, a catheter maybe inserted immediately after a procedure, or after a certain periodduring which the risk of forming vasospasms increases. For example,after a neurosurgical procedure, the risk of forming vasospasms mayincrease at or around 4 days after the procedure. Accordingly, acatheter coated with an anti-thrombotic agent may be inserted near thattime and left in for multiple days to treat the onset of a vasospasm. Itis further appreciated that other aspects of this invention, for examplethe one or more sensors as described below in reference to FIG. 3, mayfurther facilitate near instantaneous detection of a vasospasm by acatheter device already existing in the patient's vasculature.

FIG. 1B illustrates a lateral cross-section diagram of an examplecatheter device 100 taken across line 1-1. Accordingly, the catheterdevice 100 may include one or more lumens 130 existing therein. Thelumen or lumens (also known as ports) 130 may be used for fluid deliverysuch as medicinal agents, protein solutions, additional anti-thromboticagent delivery, vasodilating agent, or the like, or for delivery ofsecondary devices such as guide wires used to aid insertion, balloons orother devices used during angioplasty, sensors, or the like. It isappreciated that although FIG. 1B illustrates a single lumen, thecatheter device 100 may be configured to include multiple lumens. Thecatheter device 100 illustrated in FIG. 1B includes an anti-thromboticagent coating or layer 120.

In the illustrated embodiment, the coating 120 may be applied around theentire circumference of the elongate catheter body 110. However, it isappreciated that the anti-thrombotic agent coating 120 may only beapplied to portions of the catheter's surface, such as strips aligningaxially with the elongate catheter body 110 or in rings around all orpart of the circumference of the elongate body and positioned at one ormore portions along the length of the elongate catheter body 110. Again,the anti-thrombotic agent 120 may be applied as a coating to all or partof the exterior surface, may be impregnated in the material comprisingthe surface of the elongate catheter body 110, may be applied as part ofa matrix, such as a protein, colloid, or protein colloidal matrix,and/or may be applied to the interior surface of the catheter device 100defining the one or more lumens 130.

FIG. 2 illustrates another example embodiment of the catheter device 200including a perforated tip 210 at its distal end. The perforated tip 210may be inserted into the elongate catheter body so as to be flush withthe body, may be inserted over the elongate catheter body. Theperforated tip 210 may be rounded or substantially planar. Theperforated tip 210 may include one or more central orifices 220extending entirely through the tip and in communication with the one ormore lumens or ports of the catheter device 200, as further describedabove in reference to FIG. 1B. For example, the one or more centralorifices 220 may communicate with a lumen used with guide wireinsertion, or with a lumen used to deliver a secondary device, such as aballoon. It is appreciated that the central orifice or orifices 220 neednot align in the center of the perforated tip 210, but instead are toalign with the one or more lumens of the catheter used for objects orsubstances that are not intended to be delivered via the multipleperforated orifices. It is further appreciated that while secondarydevices or objects are described as being delivered through the centralorifice 220, fluids such as medicinal or therapeutic agents may also bedelivered through the one or more central orifices 220. It is furtherappreciated that another example embodiment may not include a centralorifice 220, and only include the multiple perforated orifices asdescribed. The perforated tip 210 further includes multiple perforatedorifices 230 extending entirely through the tip, having a diametersubstantially smaller than the overall diameter of the elongate catheterbody. The multiple perforated orifices 230 may be randomly aligned oraligned in a pattern on the perforated tip 210 for facilitating fluidflow. The multiple perforated orifices 230 may communicate with at leastone lumen existing within the catheter device 200.

The perforated tip 210 may facilitate an improved distribution of fluidflow from within the catheter device 200. Additionally, the perforatedtip 210 may allow fluid to be delivered to the site at a higher pressureand/or flow velocity. By increasing the fluid flow and/or increasing thepressure at which the fluid is delivered, clotting may also be reducedat the site. The fluid being delivered may be, in one example, a salinesolution delivered at rates between approximately 5 cc/hr andapproximately 50 cc/hr. In other examples, the fluid delivered may be avasodilator, such as verapamil, an anti-thrombotic coating, such asheparin, another anticoagulant substance, or any combination thereof. Itis appreciated that the perforated tip 210 may also be removablyattached to the catheter device 200, allowing for selective use andretrofitted adaptations of the tip to existing catheters.

FIG. 3 illustrates another example embodiment of the catheter deviceincluding at least one sensor and communicating with a controller and afluid delivery system. The catheter device 300 illustrated in FIG. 3includes at least one distal sensor device 310, which may be a pressuresensing device, affixed to the elongate catheter body 380 at or near itsdistal portion for measuring the pressure within the vessel existing ator near the site. The sensor device 310 may be affixed to the elongatecatheter body 380 so as to substantially circumscribe the body, or maybe affixed at on or more points around the circumference of the elongatecatheter body 380. Alternatively, the sensor device 310 may be a singlesensor device affixed at a single point on the elongate catheter body380. In yet another example embodiment, the distal sensor device 310 maybe affixed, at least partly, to the tip of the catheter device 300.

The distal sensor device 310 may be, for example, a pressure transducer,a strain gauge, mechanical deflection sensor,piezoresistive/semiconductor, microelctromechanical sensor, vibrationalsensor, capacitance-based sensor, fiber optic-based sensor, or the like.The distal sensor device 310 may be in electrical or mechanicalcommunication 370 (depending upon the type of pressure sensor employed)with a controller 330 for transmitting signals corresponding to apressure sensed in the vasculature. The controller 330 may becomputer-based controller, having a memory and a processor for executingsoftware and/or hardware-based instructions for catheter operations andfunctions, as described more fully herein.

Additionally, the catheter device 300 may be in fluid communication witha fluid delivery system 340 by a fluid path 360 and the controller 330may be in electrical communication with the fluid delivery system 340 bya communication link 350. The fluid delivery system may be controlled inpart by the controller to deliver fluids via the catheter device 300.The distal sensor device 310 in communication with the controller 330allows for implementing a feedback loop (or cybernetic loop) between thepressure sensed at the site (for example, the vasospasm site) and thedelivery of the agent and/or any other fluids from the fluid deliverysystem 340 to the site. For example, the greater the pressure, thegreater the delivery of the vasodilator to the site. Alternatively,sensing a decreased or a decreasing pressure at the site may cause thecontroller to deliver less vasodilator.

The catheter device may optionally include a proximal sensor device 320positioned proximally to the distal pressure sensor 310. The proximalsensor device 320 may be positioned at a position on the elongatecatheter body 380 so as to be located in the systemic vasculature of thepatient. As described above with reference to the distal sensor device310, the proximal sensor device is in communication with the controller330 for transmittal signals indicating the pressure at a second point inthe patient's vasculature. A catheter device 300 configured with twopressure sensing devices 310, 320 allows the controller 330 to perform arelative comparison of the signals representing the pressure sensed inthe vasculature at or near the procedure site and the pressure sensed atanother point in the patient's vasculature. The relative comparisonallows the controller 330 to adjust the delivery of fluid, for example avasodilator (or other medicinal agent), based at least in part on twosensed pressures. It is appreciated that the signals representing thetwo sensed pressures may be compared in many ways, for example,calculating the difference, calculating a ratio, modeling, adaptive,real-time learning, mathematical algorithms, or the like. It is alsoappreciated that the operator of the catheter device 300, for example aphysician performing the procedure, may also observe the measuredpressure at the first or both the first and the second locations asdisplayed by the controller and adjust the fluid delivery system 340manually, or alter the automatic fluid delivery manually, responsive tothe observations.

These example embodiments of a catheter device 300 including one or moresensor devices may further include an anti-thrombotic agent or otheranticoagulant coating, as is described more fully with reference toFIG. 1. The inclusion of the anti-thrombotic or anticoagulant coatingwith a catheter device having one or more sensor devices allows forinstantaneous or near-instantaneous detection of vasospasmic activities,and thus further allows for quicker provision of treatment in responsethereto.

It is appreciated that the sensor devices 310, 320 need not be pressuresensing devices. For example, the sensor devices may include anultrasonic sensor device in communication with the controller 330. Theultrasonic sensor device may be used to monitor blood flow at or nearthe site, which may be indicative of the presence and/or severity of avasospasm in the vessel. As described in reference to the pressuresensing devices, the signals obtained from the ultrasonic monitoringdevice representing blood flow may be supplied to the controller 330 foradjusting the delivery of fluid by the fluid delivery device 340.Further, it is appreciated that the signals from any alternative sensordevices may also be displayed, graphically and/or numerically, to theuser by the controller 330.

FIG. 4 illustrates an example method by which an embodiment of thecatheter device may operate. Provided is a flowchart 400 illustratingthe sensing of a condition at one or more locations in the vasculatureand controlling fluid delivery in response thereto, as is described inreference to FIG. 3. In one example, as described above, the conditionmay be pressure within the vessel, and pressure will be used as theexemplary condition with reference to the method described in FIG. 4.However, it is appreciated that other conditions may be sensed, inaddition to or alternatively, and the fluid delivery may be controlledin much the same manner. For example, blood flow may be an alternativecondition sensed.

At block 410, pressure is measured at at least one location in thevessel in which the catheter is positioned by one or more sensordevices. The sensor device may be a pressure transducer, or the like.Furthermore, in some example embodiments, the pressure may be sensed attwo locations—at or near the distal portion of the catheter (e.g.,distal sensor device) and proximal to that portion (e.g., proximalsensor device)—allowing for a comparison of the two pressures forcontrolling fluid delivery.

Block 420 follows block 410, in which a signal is transmitted from theone or more pressure sensor devices to a controller. The signaltransmitted may be a raw digital signal which may be operated on togenerate meaningful units at the controller, as is known.

Block 430 follows block 420, in which the controller performs ananalysis on the one or more signals received from the sensor device. Forexample, if the catheter device includes one sensor device—a distalsensor device—the controller may simply compare the pressure to knownpressure ranges to determine whether the pressure is within anacceptable range. Alternatively, the controller may compare topreviously received and stored pressure measurements to determine thedirection in which the pressure is moving. If the catheter deviceincludes two sensor devices—a distal sensor device and a proximal sensordevice—the analysis performed at block 430 may include comparing betweenthe two pressures sensed, as described above.

Block 440 follows block 430, in which the fluid delivered through thecatheter device is adjusted based at least in part on the analysis ofsignals received from the one or more sensor devices, as performed atblock 430. In one embodiment, the controller may automatically performthe adjustment responsive to the analysis performed. In anotherembodiment, the operator of the catheter, for example a physician, mayperform the adjustment based upon a display of the result of theanalysis performed at block 430 and/or a display of the conditionmeasurement corresponding to the signal transmitted from the sensordevices. It is also appreciated that while the fluid delivery may beautomatically controlled by the controller, an operator may also adjustthe delivery manually. An example of adjusting the fluid delivery asperformed at block 440 may be increasing the delivery of a vasodilatorwhen the analysis determines the pressure is increasing, or decreasingthe delivery of the vasodilator when the analysis determines that thepressure is decreasing.

In another example including a distal sensor device and a proximalsensor device, the analysis performed at block 430 may result in a ratiocomparing the signals transmitted from the distal sensor device to thesignals transmitted from the proximal sensor device, whereby if theratio is over a predefined number (e.g., greater than around 1:1), thenthe controller causes the fluid delivery device to deliver greateramounts of vasodilating fluid to the site. Similarly, if the ratio islower than a predefined number, then the controller may reduce or haltthe delivery of vasodilating fluid to the site. The controller mayfurther include instructions that allow increases the rate at which thefluid is delivered based on the signals received from the one or moresensor devices. For example, the greater the disparity between thesignal from the distal sensor device and the signal from the proximalsensor device, the greater the rate the controller causes the fluiddelivery device to deliver vasodilating fluid. It is appreciated thatthe predefined limits or thresholds may be predetermined during themanufacture and/or configuration of the catheter device, or may be setby an operator or configurator after manufacture and before or duringuse. Furthermore, any predefined limits or thresholds for use in theanalysis may be adjustable and set through an interface or the like.

References are made to block diagrams of systems, methods, apparatuses,and computer program products according to example embodiments of theinvention. It will be understood that at least some of the blocks of theblock diagrams, and combinations of blocks in the block diagrams,respectively, may be implemented at least partially by computer programinstructions. These computer program instructions may be loaded onto ageneral purpose computer, special purpose computer, special purposehardware-based computer, or other programmable data processing apparatusto produce a machine, such that the instructions which execute on thecomputer or other programmable data processing apparatus create meansfor implementing the functionality of at least some of the blocks of theblock diagrams, or combinations of blocks in the block diagramsdiscussed.

These computer program instructions may also be stored in acomputer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory produce an article of manufacture including instruction meansthat implement the function specified in the block or blocks. Thecomputer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational elements to be performed on the computer or otherprogrammable apparatus to produce a computer implemented process suchthat the instructions that execute on the computer or other programmableapparatus provide elements for implementing the functions specified inthe block or blocks.

One or more components of the systems and one or more elements of themethods described herein may be implemented through an applicationprogram running on an operating system of a computer. They also may bepracticed with other computer system configurations, including hand-helddevices, multiprocessor systems, microprocessor based, or programmableconsumer electronics, mini-computers, mainframe computers, etc.

Application programs that are components of the systems and methodsdescribed herein may include routines, programs, components, datastructures, etc. that implement certain abstract data types and performcertain tasks or actions. In a distributed computing environment, theapplication program (in whole or in part) may be located in localmemory, or in other storage. In addition, or in the alternative, theapplication program (in whole or in part) may be located in remotememory or in storage to allow for circumstances where tasks areperformed by remote processing devices linked through a communicationsnetwork.

Many modifications and other embodiments of the invention set forthherein to which these descriptions pertain will come to mind having thebenefit of the teachings presented in the foregoing descriptions and theassociated drawings. Thus, it will be appreciated that the invention maybe embodied in many forms and should not be limited to the exampleembodiments described above. Therefore, it is to be understood that theinvention is not to be limited to the specific embodiments disclosed andthat modifications and other embodiments are intended to be includedwithin the scope of the appended claims. Although specific terms areemployed herein, they are used in a generic and descriptive sense onlyand not for purposes of limitation.

What is claimed is:
 1. A catheter device, comprising: an elongatecatheter body, comprising a distal end and a proximal end; at least onelumen extending from the proximal end to the distal end of the elongatecatheter body; a distal sensor device affixed to the elongate catheterbody substantially near the distal end, wherein the distal sensor devicegenerates a signal that is a distal pressure; a controller incommunication with the distal sensor device, and a fluid delivery devicein fluid communication with the at least one lumen and in electricalcommunication with the controller; wherein said catheter device is acerebral catheter device configured to be inserted into cerebralarteries; wherein the controller is configured to store one or moresignals collected over time as historical signals corresponding to oneor more historical distal pressure measurements and to perform ananalysis comprising comparing: the signal generated from the distalsensor device to the historical signals and determine whether the firstsignal is greater than or lower than at least one of the historicalsignals, and cause an (a) increase in fluid delivery to the at least onelumen from the fluid delivery device if the distal pressure is at afirst predefined limit greater than at least one of the historicaldistal pressures, or (b) decrease in fluid delivery to the at least onelumen from the fluid delivery device if the distal pressure is at asecond predefined limit lower than at least one of the historicalpressures.
 2. The catheter device of claim 1, wherein the analysisperformed by the controller comprises determining a ratio of the distalpressure to at least one of the historical distal pressures, and whereinif the ratio is at or exceeds a first predefined ratio limit, the fluiddelivery is adjusted to be increased, and wherein if the ratio is belowa second predefined ratio limit, the fluid delivery is adjusted to bedecreased.
 3. The catheter device of claim 2, wherein the firstpredefined ratio limit and the second predefined ratio limit comprisethe same value.
 4. The catheter device of claim 1, wherein the fluiddelivery device delivers a fluid comprising at least a saline solutioncomprising a vasodilator, an anti-thrombotic agent, an antibiotic, achemotherapeutic agent, other suitable therapeutic agent, or combinationthereof.
 5. The catheter device of claim 1, further comprising ananti-thrombotic agent at least partially coated or deposited thereon. 6.The catheter device of claim 5, wherein the anti-thrombotic agentcomprises a coating applied to substantially an entire surface of theelongate catheter body.
 7. The catheter device of claim 5, wherein theanti-thrombotic agent is at least partially impregnated into theelongate catheter body.
 8. The catheter device of claim 5, wherein theanti-thrombotic agent is deposited at least partially in an interiorsurface of the catheter device comprising the at least one lumen.
 9. Thecatheter device of claim 5, wherein the anti-thrombotic agent is timereleasable.
 10. The catheter device of claim 1, wherein the distal endof the catheter device further comprises a perforated tip affixedthereon, wherein the perforated tip comprises a rounded or substantiallyplanar surface on a distal end of the perforated tip, and a plurality ofperforated orifices on the rounded or substantially planar surface andextending through the perforated tip and in fluid communication with theat least one lumen.
 11. The catheter device of claim 10, wherein the atleast one lumen comprises a first and a second lumen, wherein theplurality of perforated orifices further comprise at least one centralorifice in communication with the first lumen, and wherein the pluralityof perforated orifices other than the at least one central orifice arein fluid communication with the second lumen.
 12. The catheter device ofclaim 11, further comprising a secondary medical device passed throughthe first lumen and the at least one central orifice, wherein thesecondary medical device comprises one of a guide wire and a balloon.13. The catheter device of claim 10, wherein a fluid is deliveredthrough the at least one lumen and the plurality of perforated orifices,wherein the fluid comprises at least one of a saline solution comprisinga vasodilator, an anti-thrombotic agent, an antibiotic, achemotherapeutic agent, other suitable therapeutic agent, or combinationthereof.
 14. The catheter device of claim 4, wherein saidanti-thrombotic agent is selected from the group consisting of heparin,warfarin, synthetic pentasaccharide inhibitors of factor Xa, andderivatives thereof.
 15. The catheter device of claim 4, wherein saidvasodilator is verapamil.
 16. A method for preventing and treatingvasospasm using the catheter device of claim
 1. 17. The method of claim16, wherein said catheter device is used in conjunction with a bloodflow transducer operable to detect a blood flow velocity and a presenceof vasospasm.
 18. The method of claim 17, wherein said blood flowtransducer is an ultrasonic monitoring device.
 19. The method of claim17, wherein said blood flow transducer is implanted, recessed into,screwed onto, or temporarily attached to the patient's skull.
 20. Themethod of claim 17, wherein the blood flow velocity obtained from theblood flow transducer is supplied to the controller for adjustingdelivery of a therapeutic fluid comprising a desired therapeutic agent.21. A method for treating neoplasm using the catheter device of claim 1.22. The method of claim 21, wherein said neoplasm is brainglioblastomas.
 23. The catheter device of claim 1, wherein thecontroller includes instructions to increase a rate of the fluiddelivery based on the distal signal and at least one of the one of thehistorical distal signals.
 24. The catheter device of claim 23, whereinthe rate of fluid delivery increase is proportional to a differencebetween the signal from the distal sensor device and at least one of thehistorical distal signals.
 25. The catheter device of claim 10, whereinthe perforated tip is inserted into or is inserted over the elongatecatheter body.